Atezolizumab +/− Selinexor for Sarcoma

Recruiting at 15 trial locations

Age: Any Age

Sex: Any

Trial Phase: Phase 2

Sponsor: National Cancer Institute (NCI)

Must not be taking: Immunosuppressants, Immunostimulants

Disqualifiers: Pregnancy, CNS metastases, Autoimmune disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Breakthrough Therapy This drug has been fast-tracked for approval by the FDA given its high promise

Compensation: Varies

Number of Visits: 28

Duration: Up to 2 years

27 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial examines whether a combination of atezolizumab and selinexor can shrink tumors in individuals with alveolar soft part sarcoma, a challenging cancer to treat. Atezolizumab, an immunotherapy, aids the immune system in fighting cancer, while selinexor inhibits cancer cell growth by blocking a specific protein. Eligible participants should have alveolar soft part sarcoma that cannot be cured with surgery and has not responded to prior immunotherapy. As a Phase 2 trial, this research focuses on assessing the treatment's effectiveness in an initial, smaller group of participants.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain medications before starting. You must not have had chemotherapy or radiotherapy within 4 weeks before the study, and you should not be on systemic immunosuppressive medications within 2 weeks prior to starting. If you're on other cancer treatments, you need to stop them at least 4 weeks before the trial begins.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the combination of atezolizumab and selinexor has been tested for safety and tolerance in patients with soft tissue sarcomas. In these studies, patients received both drugs to assess their ability to handle the treatment. The combination was generally well-tolerated, with some patients experiencing side effects, which is common in cancer treatments. These side effects were manageable and did not halt the study.

Atezolizumab is already approved for other cancers, indicating a known safety profile. Selinexor, a newer drug, has shown promise in stopping tumor growth. Together, these drugs aim to help the immune system fight cancer and prevent its spread. While side effects can occur, the research so far supports the safety of this combination in human trials. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about atezolizumab and selinexor for sarcoma because these treatments offer a fresh approach to tackling the disease. Atezolizumab is an immunotherapy drug, which works by blocking a protein called PD-L1, helping the immune system recognize and fight cancer cells more effectively. On the other hand, selinexor is a novel type of drug known as a selective inhibitor of nuclear export (SINE), which disrupts the cancer cell's ability to regulate proteins that control cell growth and survival. This combination targets sarcoma in a way that differs from traditional chemotherapy, potentially leading to more effective and targeted treatment options.

What evidence suggests that atezolizumab and selinexor might be effective treatments for sarcoma?

This trial will evaluate the combination of atezolizumab and selinexor for treating sarcoma. Studies have shown that this combination may help shrink tumors and stabilize cancer in patients with alveolar soft part sarcoma. Earlier research demonstrated that atezolizumab alone helped shrink tumors in about 24% of cases. Selinexor blocks a protein that aids cancer cell growth, potentially stopping their spread. Evidence from similar treatments suggests that selinexor can reduce the risk of disease progression or death by about 30%. Together, these drugs might offer a new approach to managing and treating this rare type of cancer. ^{2 3 6 7 8}

Who Is on the Research Team?

Alice P Chen

Principal Investigator

National Cancer Institute LAO

Are You a Good Fit for This Trial?

Adults (18+) with alveolar soft part sarcoma, a rare cancer, who can't be cured by surgery. They should have measurable tumor growth and acceptable organ function. HIV-positive patients must have an undetectable viral load on therapy. Participants need to agree to use contraception if applicable and provide biopsy samples for research.

Inclusion Criteria

Ability to understand and the willingness to sign a written informed consent document

Absolute neutrophil count >= 1,500/mcL

My kidney function, measured by creatinine levels or clearance, is within the required range.

Exclusion Criteria

History of severe allergic, anaphylactic, or other hypersensitivity reactions to specific compounds

I had mild or moderate infection symptoms within the last 2 weeks.

I have had treatment for any painful cancer spots before joining.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Safety Run-in

Initial phase to assess the safety of selinexor in combination with atezolizumab

4 weeks

Treatment

Patients receive atezolizumab and selinexor or atezolizumab alone in 28-day cycles

Up to 2 years

Visits every 28 days for treatment and assessments

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Atezolizumab
• Selinexor

Trial Overview The trial is testing the effectiveness of Atezolizumab alone or combined with Selinexor against standard treatments for shrinking tumors in alveolar soft part sarcoma. It explores how these drugs might help the immune system fight cancer or block proteins that aid in cancer cell growth.

How Is the Trial Designed?

Group I: Treatment (atezolizumab, selinexor) Experimental Treatment 6 Interventions

Patients receive atezolizumab IV over 30-60 minutes on day 8 of cycle 1, and then on day 1 of subsequent cycles. Patients also receive selinexor PO on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients also undergo ECHO during screening and CT and collection of blood samples throughout the study. Adult patients also undergo biopsies throughout the study.

Atezolizumab is already approved in United States, European Union for the following indications:

Approved in United States as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Approved in European Union as Tecentriq for:

• Melanoma
• Hepatocellular carcinoma
• Small cell lung cancer
• Non-small cell lung cancer
• Urothelial carcinoma

Who Is Running the Clinical Trial?

National Cancer Institute (NCI)

Lead Sponsor

Trials

14,080

Recruited

41,180,000+

Published Research Related to This Trial

Atezolizumab (Tecentriq) is an FDA-approved treatment for unresectable or metastatic alveolar soft part sarcoma (ASPS), showing a 24% overall response rate in a clinical trial with 49 patients, and a durable response rate of 67% at 6 months and 42% at 12 months.

The treatment has a manageable safety profile, with common severe side effects including musculoskeletal pain (8%) and hypertension (6%), making it a viable option for patients with limited treatment alternatives for this high-risk disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab as the First Systemic Therapy Approved for Alveolar Soft Part Sarcoma. Bergsma, EJ., Elgawly, M., Mancuso, D., et al.[2023]

In a real-world study of 1002 patients with previously treated non-small cell lung cancer (NSCLC), atezolizumab showed an 18-month overall survival rate of 41.1%, confirming its effectiveness outside of clinical trial settings.

The safety profile was acceptable, with an overall adverse event rate of 43.9% and immune-related adverse events at 19.0%, but caution is advised for patients with poorer performance status (ECOG ≥ 2), as they had a significantly lower survival rate of 14.3%.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effectiveness and Safety of Atezolizumab Monotherapy in Previously Treated Japanese Patients With Unresectable Advanced or Recurrent NSCLC: A Multicenter, Prospective, Observational Study (J-TAIL). Miura, S., Nishio, M., Akamatsu, H., et al.[2023]

Atezolizumab, a PD-L1 blocking antibody, shows higher rates of objective response, progression-free survival, and overall survival when used as a first-line therapy in chemotherapy-naïve patients with metastatic non-small cell lung cancer (NSCLC), compared to its use in later treatment lines.

The review included 15 ongoing studies, with 5 reporting results, indicating that atezolizumab is being explored in various treatment combinations and settings, suggesting its potential as a versatile first-line treatment option for NSCLC.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab for the First-Line Treatment of Non-small Cell Lung Cancer (NSCLC): Current Status and Future Prospects. Ryu, R., Ward, KE.[2023]

Atezolizumab significantly improved overall survival in patients with previously treated non-small-cell lung cancer compared to docetaxel, with median survival times of 13.8 months versus 9.6 months, respectively.

The safety profile of atezolizumab was favorable, with only 15% of patients experiencing grade 3 or 4 adverse events, compared to 43% in the docetaxel group, indicating it may be a safer treatment option.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab versus docetaxel in patients with previously treated non-small-cell lung cancer (OAK): a phase 3, open-label, multicentre randomised controlled trial. Rittmeyer, A., Barlesi, F., Waterkamp, D., et al.[2022]

Atezolizumab, an anti-PD-L1 antibody used for treating advanced cancers like metastatic non-small cell lung cancer, has a low incidence of cutaneous side effects, with only 20% of patients experiencing mild rashes that did not require treatment.

There have been no reported cases of severe skin reactions such as Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) associated with atezolizumab, suggesting a favorable safety profile for dermatological side effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Atezolizumab-Induced Stevens-Johnson Syndrome in a Patient with Non-Small Cell Lung Carcinoma. Chirasuthat, P., Chayavichitsilp, P.[2020]

Atezolizumab, a monoclonal antibody targeting PD-L1, has shown significant improvements in progression-free and overall survival in patients with advanced non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC) when combined with chemotherapy, as demonstrated in the IMpower studies.

The safety profile of atezolizumab in combination with chemotherapy is acceptable, with common immune-related adverse events including rash (18-28%), hypothyroidism (8-15%), and hepatitis (5-17%), consistent with its known effects as a single agent, indicating no new safety concerns.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The safety of atezolizumab plus chemotherapy for the treatment of metastatic lung cancer. Manzo, A., Carillio, G., Montanino, A., et al.[2022]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05333458

Study Details | NCT05333458 | Testing Atezolizumab With ... Giving atezolizumab in combination with selinexor may help shrink tumors and stabilize the cancer in patients with alveolar soft part sarcoma. Detailed ...

2. asco.org asco.org/abstracts-presentations/ABSTRACT449192

Safety and toxicity evaluation of the combination ... Safety and toxicity evaluation of the combination of selinexor with atezolizumab in patients with soft tissue sarcomas. ; Leukopenia*, 3 (50), 1, 2 ; Vomiting*, 3 ...

3. mdanderson.org mdanderson.org/patients-family/diagnosis-treatment/clinical-trials/clinical-trials-index/clinical-trials-detail.ID2023-0456.html

A phase 2 study of Atezolizumab with Selinexor in alveolar ... Giving atezolizumab in combination with selinexor may help shrink tumors and stabilize the cancer in patients with alveolar soft part sarcoma. Resources and ...

4. targetedonc.com targetedonc.com/view/advancing-the-treatment-of-alveolar-soft-part-sarcoma

Advancing the Treatment of Alveolar Soft Part Sarcoma The findings showed that at the 1200 mg. dose for adult and 15 mg for children, atezolizumab achieved an objective response rate of 24% (95 CI, ...

5. investors.karyopharm.com investors.karyopharm.com/2020-11-20-Karyopharm-Reports-Positive-Phase-3-SEAL-Data-in-Oral-Presentation-at-The-Connective-Tissue-Oncology-Society-2020-Annual-Meeting

Karyopharm Reports Positive Phase 3 SEAL Data in Oral ... These data indicate that treatment with XPOVIO reduced the risk of disease progression or death by approximately 30%, compared to placebo. The ...

6. ascopubs.org ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.11557

Safety and toxicity evaluation of the combination ... We designed a randomized phase 2 study to evaluate atezolizumab with or without selinexor in adult patients with ASPS that included a safety run-in (SR) open ...

7. clinicaltrials.gov clinicaltrials.gov/study/NCT05333458?term=AREA%5BConditionSearch%5D(Sarcoma)%20AND%20AREA%5BInterventionSearch%5D(Selinexor)&rank=9

Testing Atezolizumab With Selinexor in People ≥ 12 Years Old ... In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical ...

8. researchgate.net researchgate.net/publication/381417751_Safety_and_toxicity_evaluation_of_the_combination_of_selinexor_with_atezolizumab_in_patients_with_soft_tissue_sarcomas

Safety and toxicity evaluation of the combination of selinexor with ... Safety and toxicity evaluation of the combination of selinexor with atezolizumab in patients with soft tissue sarcomas. · Abstract · No full-text available.